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Experimental Biology and Medicine 226:766-775 (2001)
© 2001 Society for Experimental Biology and Medicine


ORIGINAL ARTICLE

Retinoic Acid Combined with Neurotrophin-3 Enhances the Survival and Neurite Outgrowth of Embryonic Sympathetic Neurons

Lori A. Plum*,{dagger}, Luis F. Parada{dagger}, Pantelis Tsoulfas§,2 and Margaret Clagett-Dame*,{dagger},1

* Interdepartmental Graduate Program in Nutritional Sciences and
{dagger} Department of Biochemistry and School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin 53706;
{dagger} Center for Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75235–9133;
§ Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892–4092

Both nerve growth factor (NGF) and neurotrophin-3 (NT-3) are necessary for the survival of embryonic sympathetic neurons in vivo. All-trans retinoic acid (atRA) has been shown to promote neurite outgrowth and long-term survival of chick embryonic sympathetic neurons cultured in the presence of NGF. The present study shows that atRA can also potentiate the survival and neurite outgrowth-promoting activities of NT-3. This was accomplished by enhancing the survival of existing neurons, as cell proliferation was unaffected by exposure to atRA. atRA also enhanced neurite outgrowth of the NT-3-treated cells; however, the neurites appeared thicker and less branched than cells treated with atRA in combination with NGF. Using a quantitative PCR assay, trkA and p75NTR mRNAs, but not trkC mRNA, were increased (~1.5- to 2-fold) after 72 and 48 hr of exposure of the cultures to atRA, respectively. The atRA-induced increase in trkA mRNA may play a role in the enhanced survival of neurons cultured in the presence of either NGF or NT-3, as both neurotrophins have been shown to signal through this receptor. The time course of these mRNA changes would indicate that atRA does not regulate the neurotrophin receptor mRNA directly, rather, intervening gene transcription is required. Thus, during development, atRA may play a role in fine-tuning embryonic responsiveness to both NT-3 and NGF.

Key Words: neurotrophin-3 • retinoic acid • nerve growth factor • TrkA • p75NTR • sympathetic neuron




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[Abstract] [Full Text] [PDF]




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